A Major objective of this work is to study the reversal of the degenerative changes of denervated skeletal muscle brought about by reinnervation or pharmacologic manipulation of the neuromuscular system. Recovery of muscle properties during reinnervation will be compared in the fast twitch-extensor digitorum longus and the slow-stitch soleus muscles of the rat. This process will be compared to that seen in the normal differentiation of these muscles in neonates. Recent studies from this laboratory show that acute activation of the B2-receptor adenylate cyclase system of muscle reverses some of the changes produced by denervation. Animals will now be treated chronically with selective B2 agonists after crush of the muscle nerves. It is anticipated that such treatment will depress the degenerative responses of muscle to denervation and thus facilitate the recovery of muscular function during reinnervation. During the course of these studies various molecular aspects of neuromuscular transmission will also be investigated.